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Reporting Bias is Highly Prevalent in Systematic Reviews and Meta-Analyses of Platelet Rich Plasma Injections for Hip Osteoarthritis
Kim, D., Bashrum, B. S., Kotlier, J. L., Mayfield, C. K., Thompson, A. A., Abu-Zahra, M., Hwang, M., Bolia, I. K., Petrigliano, F. A., Liu, J. N.
Arthroscopy, sports medicine, and rehabilitation. 2024;6(1):100851
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Abstract
PURPOSE To describe the incidence and types of spin in systematic reviews of platelet-rich plasma (PRP) injections for hip osteoarthritis (OA) and to determine whether patterns in study characteristics could be identified among studies with identifiable spin. METHODS The PubMed, Scopus, and SPORTDiscus databases were queried. Inclusion criteria were systematic reviews or meta-analyses that included an assessment of intra-articular PRP injections as a stand-alone treatment for hip OA. Two authors independently assessed the presence of spin in the included studies and recorded general study characteristics. The prevalence of the 15 different categories of spin was quantified using descriptive statistics. RESULTS Fifteen studies met inclusion criteria for this study. All studies contained at least two types of spin (range 2-9), with a median of 2. The most common type of spin was type 14 ("Failure to report a wide confidence interval of estimates"), which was observed in 10 studies. The second most common type of spin was type 13 ("Failure to specify the direction of the effect when it favors the control intervention"), found in 6 studies. CONCLUSIONS Spin is highly prevalent in abstracts of systematic reviews of PRP in the treatment of hip OA. Several associations were found between spin types and the study characteristics of AMSTAR 2 rating, Scopus CiteScore, journal impact factor, and PROSPERO preregistration. When present, spin in the abstracts of reviewed studies tended to favor the use of PRP in hip osteoarthritis. CLINICAL RELEVANCE It is important to understand the prevalence of spin in published abstracts, especially in areas of great impact or interest, so authors and readers can have a greater awareness of this potential form of bias.
PICO Summary
Population
Patients with hip osteoarthritis (15 systematic reviews).
Intervention
Systematic review to describe the incidence and types of spin bias in systematic reviews of platelet-rich plasma injections for hip osteoarthritis and to determine whether patterns in study characteristics could be identified among studies with identifiable spin.
Comparison
Outcome
All studies contained at least two types of spin (range 2-9), with a median of 2. The most common type of spin was type 14 ("Failure to report a wide confidence interval of estimates"), which was observed in 10 studies. The second most common type of spin was type 13 ("Failure to specify the direction of the effect when it favors the control intervention"), found in 6 studies. Several associations were found between spin types and the study characteristics of AMSTAR 2 rating, Scopus CiteScore, journal impact factor, and PROSPERO preregistration.
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Efficacy and cost-effectiveness of darbepoetin alfa once every 4 weeks versus continuous erythropoietin receptor activator once every 4 weeks for anemia correction in patients with chronic kidney disease not on dialysis
Park, G. N., Lee, K. H., Moon, J. E., Choi, S. J., Park, M. Y., Kim, J. K., Yu, B. C.
Kidney research and clinical practice. 2024
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Abstract
BACKGROUND For anemia management in patients with chronic kidney disease not on dialysis, darbepoetin alfa (DA), which has a shorter half-life but is more inexpensive than continuous erythropoietin receptor activator (CERA), is preferred in Korea. This study evaluated the efficacy, safety, and cost-effectiveness of once-in-4-weeks DA compared with once-in-4-weeks CERA in patients with chronic kidney disease not on dialysis. METHODS In this randomized, prospective, non-inferiority study, 40 erythropoiesis-stimulating agent-naïve patients with chronic kidney disease not on dialysis were randomized 1:1 to the DA group and CERA group. They received the study drug once in 4 weeks during 10- or 12-week correction period and 24-week efficacy evaluation period. The primary outcomes were the mean difference in the changes in hemoglobin levels between baseline and efficacy evaluation period and hemoglobin response rates during the correction period. The secondary outcomes included differences in adverse events and costs. RESULTS DA was non-inferior to CERA for anemia correction; the mean difference in the change in hemoglobin levels between the groups was -0.070 g/dL (95% confidence interval, -0.730 to 0.590 g/dL). Hemoglobin response rates were 100% with DA and 94.1% with CERA. Adverse events were comparable. The mean cost of DA was approximately one-third that of CERA (34,100 ± 7,600 Korean won/4 weeks vs. 115,500 ± 23,600 Korean won/4 weeks; p < 0.001). CONCLUSION Once-in-4-weeks DA safely corrects anemia in erythropoiesis-stimulating agent-naïve patients with chronic kidney disease not on dialysis and is more cost-effective than once-in-4-weeks CERA.
PICO Summary
Population
Patients with chronic kidney disease not on dialysis (n= 40).
Intervention
Darbepoetin alfa (DA), (n= 20).
Comparison
Continuous erythropoietin receptor activator (CERA), (n= 20).
Outcome
The patients received the study drug once in 4 weeks during 10- or 12-week correction period and 24-week efficacy evaluation period. The primary outcomes were the mean difference in the changes in haemoglobin levels between baseline and efficacy evaluation period and haemoglobin response rates during the correction period. DA was non-inferior to CERA for anaemia correction; the mean difference in the change in haemoglobin levels between the groups was -0.070 g/dL (95% confidence interval [-0.730, 0.590 g/dL]). Haemoglobin response rates were 100% with DA and 94.1% with CERA. Adverse events were comparable. The mean cost of DA was approximately one-third that of CERA (34,100 ± 7,600 Korean won/4 weeks vs. 115,500 ± 23,600 Korean won/4 weeks).
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Kidney disease in trials of perioperative tranexamic acid
Liu, C. W., Anih, J., Lebedeva, V., Gungor, A., Wang, C., Park, L., Roshanov, P. S.
Journal of clinical anesthesia. 2024;94:111417
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Abstract
STUDY OBJECTIVE To assess how kidney disease is handled in randomized trials evaluating the safety and efficacy of perioperative tranexamic acid, and to evaluate its effects across levels of kidney function. DESIGN Systematic review and meta-analysis of randomized controlled trials. SETTING We screened studies from a previous comprehensive systematic review, and updated its search of PubMed, Embase, and Cochrane CENTRAL to July 31, 2023. PATIENTS Patients undergoing non-obstetric surgery. INTERVENTIONS Intravenous tranexamic acid compared to placebo or usual care without tranexamic acid. MEASUREMENT We summarized the handling of kidney disease in eligibility criteria, dose adjustments for kidney function, and effects of tranexamic acid on thrombotic events, seizures, and bleeding by subgroups of kidney function. MAIN RESULTS We evaluated 300 trials with 53,085 participants; 45,958 participants (86.6%) were enrolled in 228 trials (76.0%) that explicitly excluded patients with kidney disease. Definitions of kidney diseased used for exclusion varied widely. Most were non-specific and some corresponded to mild disease. Only 5 trials adjusted dosing for kidney function. Meta-analysis of two large trials found tranexamic acid unlikely to substantially increase or decrease the occurrence of thrombotic events in patients with eGFR <60 mL/min/1.73m(2) (RR, 0.95; 95% CI: 0.83 to 1.07) or ≥ 60 mL/min/1.73m(2) (RR, 1.00; 95% CI, 0.91 to 1.11; P for subgroup difference = 0.47), but both trials excluded patients with severe kidney disease. No analysis could be performed regarding seizure risk. One large trial in noncardiac surgery reported similar reduction in bleeding across subgroups of kidney function but excluded patients with creatinine clearance <30 mL/min. CONCLUSIONS The large evidence base supporting perioperative tranexamic acid suffers from broad and unjustified exclusion of patients with kidney disease. Typical perioperative dosing of tranexamic acid is likely safe and effective in patients with creatinine clearance >30 mL/min, but effects in more severe kidney disease are unknown.
PICO Summary
Population
Patients undergoing non-obstetric surgery (300 trials, n= 53,085).
Intervention
Intravenous tranexamic acid.
Comparison
Placebo or usual care without tranexamic acid.
Outcome
From all the included studies, 45,958 participants (86.6%) were enrolled in 228 trials (76.0%) that explicitly excluded patients with kidney disease. Definitions of kidney diseased used for exclusion varied widely. Most were non-specific and some corresponded to mild disease. Only 5 trials adjusted dosing for kidney function. Meta-analysis of two large trials found tranexamic acid unlikely to substantially increase or decrease the occurrence of thrombotic events in patients with estimated glomerular filtration rate <60 mL/min/1.73m(2) (RR 0.95; 95% CI [0.83, 1.07]) or ≥ 60 mL/min/1.73m(2) (RR 1.00; 95% CI [0.91, 1.11], but both trials excluded patients with severe kidney disease. No analysis could be performed regarding seizure risk. One large trial in non-cardiac surgery reported similar reduction in bleeding across subgroups of kidney function but excluded patients with creatinine clearance <30 mL/min.
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Erythropoiesis-stimulating agents and cardiovascular mortality: A systematic review and meta-analysis of 17 studies and 372,156 hemodialysis patients
Karimi, Z., Raeisi Shahraki, H., Mohammadian-Hafshejani, A.
International journal of cardiology. Cardiovascular risk and prevention. 2023;19:200220
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Abstract
INTRODUCTION Prior studies on the association between erythropoiesis-stimulating agents (ESAs) and cardiovascular mortality in hemodialysis patients have yielded conflicting findings. We aimed to clarify this relationship through a systematic review and meta-analysis of current evidence. METHODS We comprehensively searched major databases for observational and interventional studies on ESA use and cardiovascular mortality in hemodialysis patients published from 1980 to September 2023. Pooled risk ratios (RR) with 95 % confidence intervals (CI) were calculated using random-effects models. Sources of heterogeneity were explored through subgroup analyses and meta-regression. The study data were analyzed using Stata 15 software. FINDINGS Upon conducting the initial search, we extracted 792 articles and, after screening and considering the research criteria, 17 studies with 372,156 participants were included in the meta-analysis. Overall, ESA use was associated with a 27 % increased risk of cardiovascular mortality (RR 1.27, 95 % CI: 1.15-1.40, p < 0.001). This risk varied by geographical location, with RRs of 1.27 (95 % CI: 1.14-1.41; p-value≤0.001) for America, 1.33 (95 % CI: 1.12-1.58; p-value = 0.001) for Asia, and 1.23 (95 % CI: 1.02-1.49; p-value = 0.028) for Europe. Importantly, a gender disparity was revealed, with studies involving a higher proportion of males showing greater risks (RR 1.51, 95 % CI: 1.25-1.83, p < 0.001) than female-predominant studies (RR 1.08, 95 % CI: 0.86-1.36, p < 0.001). CONCLUSION Our meta-analysis indicates ESA use is associated with heightened cardiovascular mortality in hemodialysis patients, especially in males. These findings have implications for optimizing dosing strategies while balancing efficacy and safety. Further research is warranted, particularly randomized controlled trials, to establish definitive ESA dosing guidelines.
PICO Summary
Population
Haemodialysis patients (17 studies, n= 372,156).
Intervention
Systematic review and meta-analysis evaluating the relationship between erythropoiesis-stimulating agents (ESAs) use and cardiovascular mortality.
Comparison
Outcome
Overall, ESA use was associated with a 27% increased risk of cardiovascular mortality (RR, 1.27; 95% CI [1.15, 1.40]). This risk varied by geographical location, with RRs of 1.27; 95% CI [1.14, 1.41] for America, 1.33; 95% CI [1.12, 1.58] for Asia, and 1.23; 95% CI [1.02, 1.49] for Europe. A gender disparity was revealed, with studies involving a higher proportion of males showing greater risks RR, 1.51; 95% CI [1.25, 1.83] than female-predominant studies RR, 1.08; 95% CI [0.86, 1.36].
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COVID-19 Convalescent Plasma Outpatient Therapy to Prevent Outpatient Hospitalization: A Meta-analysis of Individual Participant Data From Five Randomized Trials
Levine AC, Fukuta Y, Huaman MA, Ou J, Meisenberg BR, Patel B, Paxton JH, Hanley DF, Rijnders BJ, Gharbharan A, et al
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2023
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Abstract
BACKGROUND Outpatient monoclonal antibodies are no longer effective and antiviral treatments for COVID-19 disease remain largely unavailable in many countries worldwide. Although treatment with COVID-19 convalescent plasma is promising, clinical trials among outpatients have shown mixed results. METHODS We conducted an individual participant data meta-analysis from outpatient trials to assess the overall risk reduction for all-cause hospitalizations by day 28 in transfused participants. Relevant trials were identified by searching MEDLINE, Embase, MedRxiv, World Health Organization, Cochrane Library, and Web of Science from January 2020 to September 2022. RESULTS Five included studies from four countries enrolled and transfused 2,620 adult patients. Comorbidities were present in 1,795 (69%). The virus neutralizing antibody dilutional titer levels ranged from 8 to 14,580 in diverse assays. 160 (12.2%) of 1315 control patients were hospitalized, versus 111 (8.5%) of 1305 COVID-19 convalescent plasma treated patients, yielding a 3.7% (95%CI: 1.3%-6.0%; p=.001) absolute risk reduction and 30.1% relative risk reduction for all-cause hospitalization. The hospitalization reduction was greatest in those with both early transfusion and high titer with a 7.6% absolute risk reduction (95%CI: 4.0%-11.1%; p=.0001) accompanied by at 51.4% relative risk reduction. No significant reduction in hospitalization was seen with treatment > 5 days after symptom onset or in those receiving COVID-19 convalescent plasma with antibody titers below the median titer. CONCLUSIONS Among outpatients with COVID-19, treatment with COVID-19 convalescent plasma reduced the rate of all-cause hospitalization and may be most effective when given within 5 days of symptom onset and when antibody titer is higher.
PICO Summary
Population
Adult COVID-19 outpatients (5 studies, n= 2,620).
Intervention
Intravenous COVID-19 convalescent plasma (CCP) transfusion (n= 1,305).
Comparison
Non-convalescent plasma or normal saline (n= 1,315).
Outcome
The virus neutralizing antibody dilutional titre levels ranged from 8 to 14,580 in diverse assays. 160 (12.2%) of 1,315 control patients were hospitalized, versus 111 (8.5%) of 1,305 COVID-19 convalescent plasma treated patients, yielding a 3.7% (95% CI: 1.3% - 6.0%) absolute risk reduction and 30.1% relative risk reduction for all-cause hospitalization. The hospitalization reduction was greatest in those with both early transfusion and high titre with a 7.6% absolute risk reduction (95% CI: 4.0% - 11.1%) accompanied by at 51.4% relative risk reduction. No significant reduction in hospitalization was seen with treatment > 5 days after symptom onset or in those receiving COVID-19 convalescent plasma with antibody titres below the median titre.
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Evaluating the costs and consequences of computerized clinical decision support systems in hospitals: a scoping review and recommendations for future practice
White NM, Carter HE, Kularatna S, Borg DN, Brain DC, Tariq A, Abell B, Blythe R, McPhail SM
Journal of the American Medical Informatics Association : JAMIA. 2023
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Editor's Choice
Abstract
OBJECTIVE Sustainable investment in computerized decision support systems (CDSS) requires robust evaluation of their economic impacts compared with current clinical workflows. We reviewed current approaches used to evaluate the costs and consequences of CDSS in hospital settings and presented recommendations to improve the generalizability of future evaluations. MATERIALS AND METHODS A scoping review of peer-reviewed research articles published since 2010. Searches were completed in the PubMed, Ovid Medline, Embase, and Scopus databases (last searched February 14, 2023). All studies reported the costs and consequences of a CDSS-based intervention compared with current hospital workflows. Findings were summarized using narrative synthesis. Individual studies were further appraised against the Consolidated Health Economic Evaluation and Reporting (CHEERS) 2022 checklist. RESULTS Twenty-nine studies published since 2010 were included. Studies evaluated CDSS for adverse event surveillance (5 studies), antimicrobial stewardship (4 studies), blood product management (8 studies), laboratory testing (7 studies), and medication safety (5 studies). All studies evaluated costs from a hospital perspective but varied based on the valuation of resources affected by CDSS implementation, and the measurement of consequences. We recommend future studies follow guidance from the CHEERS checklist; use study designs that adjust for confounders; consider both the costs of CDSS implementation and adherence; evaluate consequences that are directly or indirectly affected by CDSS-initiated behavior change; examine the impacts of uncertainty and differences in outcomes across patient subgroups. DISCUSSION AND CONCLUSION Improving consistency in the conduct and reporting of evaluations will enable detailed comparisons between promising initiatives, and their subsequent uptake by decision-makers.
PICO Summary
Population
Patients in hospital settings – including those receiving inpatient, emergency, or ambulatory care (29 studies).
Intervention
Computerized decision support systems (CDSS) based intervention.
Comparison
Current hospital workflows.
Outcome
Studies evaluated CDSS for adverse event surveillance (5 studies), antimicrobial stewardship (4 studies), blood product management (8 studies), laboratory testing (7 studies), and medication safety (5 studies). All studies evaluated costs from a hospital perspective but varied based on the valuation of resources affected by CDSS implementation, and the measurement of consequences.
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Standard of care versus Octreotide in Angiodysplasia-related bleeding (the OCEAN study): A Multicenter Randomized Controlled trial
Goltstein, L. C. M. J., Grooteman, K. V., Bernts, L. H. P., Scheffer, R. C. H., Laheij, R. J. F., Gilissen, L. P. L., Schrauwen, R. W. M., Talstra, N. C., Zuur, A. T., Braat, H., et al
Gastroenterology. 2023
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Abstract
BACKGROUND AND AIMS Gastrointestinal angiodysplasias are vascular anomalies that may result in transfusion-dependent anemia despite endoscopic therapy. An individual patient data meta-analysis of cohort studies suggests that octreotide decreases rebleeding rates, but component studies possessed a high risk of bias. We aimed to investigate the efficacy of octreotide in reducing the transfusion requirements of patients with angiodysplasia-related anemia in a clinical trial setting. METHODS The study was designed as a multicenter, open-label, randomized controlled trial. Patients with angiodysplasia bleeding were required to have had at least four red blood cell (RBC) units and/or parental iron infusions in the year preceding randomization. Patients were allocated (1:1) to 40mg octreotide long-acting release intramuscular every 28 days or standard of care, including endoscopic therapy. The treatment duration was one year. The primary outcome was the mean difference in the number of transfusion units (RBC + parental iron) between the octreotide and standard of care groups. Patients who received at least one octreotide injection or followed standard of care for at least one month were included in the intention-to-treat analyses. Analyses of covariance were used to adjust for baseline transfusion requirements and incomplete follow-up. RESULTS We enrolled 62 patients (mean age 72 years, 32 males) from 17 Dutch hospitals in the octreotide (n=31) and standard of care (n=31) groups. Patients required a mean number of 20.3 (SD 15.6) transfusion units and 2.4 (SD 2.0) endoscopic procedures in the year before enrolment. The total number of transfusions was lower with octreotide (11.0; 95% CI, 5.5-16.5) compared to standard of care (21.2; 95% CI, 15.7-26.7). Octreotide reduced the mean number of transfusion units by 10.2 (95% CI, 2.4-18.1; P = .012). Octreotide reduced the annual volume of endoscopic procedures by 0.9 (95% CI, 0.3-1.5). CONCLUSION Octreotide effectively reduces transfusion requirements and the need for endoscopic therapy in patients with angiodysplasia-related anemia. CLINICALTRIALS gov, NCT02384122.
PICO Summary
Population
Patients with refractory anemia due to bleeding gastrointestinal angiodysplasias, enrolled in the OCEAN randomised controlled trial (n= 62).
Intervention
Octreotide (n= 31).
Comparison
Standard of care (n= 31).
Outcome
The treatment duration was one year. The primary outcome was the mean difference in the number of transfusion units (red blood cell + parental iron) between the octreotide and standard of care groups. The total number of transfusions was lower with octreotide (11.0; 95% CI [5.5, 16.5]) compared to standard of care (21.2; 95% CI [15.7, 26.7]). Octreotide reduced the mean number of transfusion units by 10.2; 95% CI [2.4, 18.1]. Octreotide reduced the annual volume of endoscopic procedures by 0.9; 95% CI [0.3, 1.5].
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Efficacy of Ferric carboxymaltose in heart failure with iron deficiency: an individual patient data meta-analysis
Ponikowski, P., Mentz, R. J., Hernandez, A. F., Butler, J., Khan, M. S., van Veldhuisen, D. J., Roubert, B., Blackman, N., Friede, T., Jankowska, E. A., et al
European heart journal. 2023
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Abstract
BACKGROUND AND AIMS Whereas a beneficial effect of intravenous ferric carboxymaltose (FCM) on symptoms and exercise capacity among patients with iron deficiency (ID) and heart failure (HF) has been consistently demonstrated, the effects of treatment on clinical events remain the subject of research. This meta-analysis aimed to characterize the effects of FCM therapy on hospitalizations and mortality. METHODS Patient-level data from randomized, placebo-controlled FCM trials including adults with HF and ID with ≥52 weeks follow-up were analysed. The co-primary efficacy endpoints were (1) composite of total/recurrent cardiovascular hospitalizations and cardiovascular death, and (2) composite of total HF hospitalizations and cardiovascular death, through 52 weeks. Key secondary endpoints included individual composite endpoint components. Event rates were analysed using a negative binomial model. Treatment-emergent adverse events were also examined. RESULTS Three FCM trials with a total of 4501 patients were included. FCM was associated with a significantly reduced risk of co-primary endpoint 1 (rate ratio [RR] 0.86; 95% confidence interval [CI] 0.75-0.98; P=0.029; Cochran Q: 0.008), with a trend towards a reduction of co-primary endpoint 2 (RR 0.87; 95% CI 0.75-1.01; P=0.076; Cochran Q: 0.024). Treatment effects appeared to result from reduced hospitalization rates, not improved survival. Treatment appeared to have a good safety profile and was well-tolerated. CONCLUSIONS In iron-deficient patients with HF with reduced left ventricular ejection fraction, intravenous FCM was associated with significantly reduced risk of hospital admissions for HF and cardiovascular causes, with no apparent effect on mortality.
PICO Summary
Population
Adults with heart failure (HF) and iron deficiency enrolled in the ferric carboxymaltose (FCM) trials: CONFIRM-HF, AFFIRM-AHF, and HEART-FID (3 randomised controlled trials, n= 4,501).
Intervention
FCM (n= 2,251).
Comparison
Placebo (n= 2,250).
Outcome
The co-primary efficacy endpoints were (1) composite of total/recurrent cardiovascular hospitalizations and cardiovascular death, and (2) composite of total HF hospitalizations and cardiovascular death, through 52 weeks. FCM was associated with a significantly reduced risk of co-primary endpoint 1 (rate ratio [RR] 0.86; 95% confidence interval (CI) [0.75, 0.98]; Cochran Q: 0.008), with a trend towards a reduction of co-primary endpoint 2 (RR 0.87; 95% CI [0.75, 1.01]; Cochran Q: 0.024).
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Plasmapheresis to remove amyloid fibrin(ogen) particles for treating the post-COVID-19 condition
Fox, T., Hunt, B. J., Ariens, R. A., Towers, G. J., Lever, R., Garner, P., Kuehn, R.
The Cochrane database of systematic reviews. 2023;7(7):Cd015775
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Abstract
BACKGROUND The post-COVID-19 condition (PCC) consists of a wide array of symptoms including fatigue and impaired daily living. People seek a wide variety of approaches to help them recover. A new belief, arising from a few laboratory studies, is that 'microclots' cause the symptoms of PCC. This belief has been extended outside these studies, suggesting that to recover people need plasmapheresis (an expensive process where blood is filtered outside the body). We appraised the laboratory studies, and it was clear that the term 'microclots' is incorrect to describe the phenomenon being described. The particles are amyloid and include fibrin(ogen); amyloid is not a part of a thrombus which is a mix of fibrin mesh and platelets. Initial acute COVID-19 infection is associated with clotting abnormalities; this review concerns amyloid fibrin(ogen) particles in PCC only. We have reported here our appraisal of laboratory studies investigating the presence of amyloid fibrin(ogen) particles in PCC, and of evidence that plasmapheresis may be an effective therapy to remove amyloid fibrin(ogen) particles for treating PCC. OBJECTIVES Laboratory studies review To summarize and appraise the research reports on amyloid fibrin(ogen) particles related to PCC. Randomized controlled trials review To assess the evidence of the safety and efficacy of plasmapheresis to remove amyloid fibrin(ogen) particles in individuals with PCC from randomized controlled trials. SEARCH METHODS Laboratory studies review We searched for all relevant laboratory studies up to 27 October 2022 using a comprehensive search strategy which included the search terms 'COVID', 'amyloid', 'fibrin', 'fibrinogen'. Randomized controlled trials review We searched the following databases on 21 October 2022: Cochrane COVID-19 Study Register; MEDLINE (Ovid); Embase (Ovid); and BIOSIS Previews (Web of Science). We also searched the WHO International Clinical Trials Registry Platform and ClinicalTrials.gov for trials in progress. SELECTION CRITERIA Laboratory studies review Laboratory studies that investigate the presence of amyloid fibrin(ogen) particles in plasma samples from patients with PCC were eligible. This included studies with or without controls. Randomized controlled trials review Studies were eligible if they were of randomized controlled design and investigated the effectiveness or safety of plasmapheresis for removing amyloid fibrin(ogen) particles for treating PCC. DATA COLLECTION AND ANALYSIS Two review authors applied study inclusion criteria to identify eligible studies and extracted data. Laboratory studies review We assessed the risk of bias of included studies using pre-developed methods for laboratory studies. We planned to perform synthesis without meta-analysis (SWiM) as described in our protocol. Randomized controlled trials review We planned that if we identified any eligible studies, we would assess risk of bias and report results with 95% confidence intervals. The primary outcome was recovery, measured using the Post-COVID-19 Functional Status Scale (absence of symptoms related to the illness, ability to do usual daily activities, and a return to a previous state of health and mind). MAIN RESULTS Laboratory studies review We identified five laboratory studies. Amyloid fibrin(ogen) particles were identified in participants across all studies, including those with PCC, healthy individuals, and those with diabetes. The results of three studies were based on visual images of amyloid fibrin(ogen) particles, which did not quantify the amount or size of the particles identified. Formal risk of bias assessment showed concerns in how the studies were conducted and reported. This means the results were insufficient to support the belief that amyloid fibrin(ogen) particles are associated with PCC, or to determine whether there is a difference in the amount or size of amyloid fibrin(ogen) particles in the plasma of people with PCC compared to healthy controls. Randomized controlled trials review We identified no trials meeting our inclusion criteria. AUTHORS' CONCLUSIONS In the absence of reliable research showing that amyloid fibrin(ogen) particles contribute to the pathophysiology of PCC, there is no rationale for plasmapheresis to remove amyloid fibrin(ogen) particles in PCC. Plasmapheresis for this indication should not be used outside the context of a well-conducted randomized controlled trial.
PICO Summary
Population
Any person diagnosed with post‐COVID‐19 condition (PCC), (5 laboratory studies).
Intervention
Plasmapheresis performed with the intention of removing amyloid fibrin(ogen) particles.
Comparison
Placebo or standard of care.
Outcome
No randomised controlled trials or ongoing trials where patients with PCC had undergone plasmapheresis with the intention of removing amyloid fibrin(ogen) particles were found. Five laboratory studies that assessed whether amyloid fibrin(ogen) particles were present in the blood of patients with post‐COVID‐19 condition were included. Amyloid fibrin(ogen) particles were identified in participants across the included studies, including those with PCC, healthy individuals, and those with diabetes. The results of three studies were based on visual images of amyloid fibrin(ogen) particles, which did not quantify the amount or size of the particles identified. Formal risk of bias assessment showed concerns in how the studies were conducted and reported. This means the results were insufficient to support the belief that amyloid fibrin(ogen) particles are associated with PCC, or to determine whether there is a difference in the amount or size of amyloid fibrin(ogen) particles in the plasma of people with PCC compared to healthy controls.
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10.
Convalescent Plasma for Covid-19-Induced ARDS in Mechanically Ventilated Patients
Misset, B., Piagnerelli, M., Hoste, E., Dardenne, N., Grimaldi, D., Michaux, I., De Waele, E., Dumoulin, A., Jorens, P. G., van der Hauwaert, E., et al
The New England journal of medicine. 2023;389(17):1590-1600
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Editor's Choice
Abstract
BACKGROUND Passive immunization with plasma collected from convalescent patients has been regularly used to treat coronavirus disease 2019 (Covid-19). Minimal data are available regarding the use of convalescent plasma in patients with Covid-19-induced acute respiratory distress syndrome (ARDS). METHODS In this open-label trial, we randomly assigned adult patients with Covid-19-induced ARDS who had been receiving invasive mechanical ventilation for less than 5 days in a 1:1 ratio to receive either convalescent plasma with a neutralizing antibody titer of at least 1:320 or standard care alone. Randomization was stratified according to the time from tracheal intubation to inclusion. The primary outcome was death by day 28. RESULTS A total of 475 patients underwent randomization from September 2020 through March 2022. Overall, 237 patients were assigned to receive convalescent plasma and 238 to receive standard care. Owing to a shortage of convalescent plasma, a neutralizing antibody titer of 1:160 was administered to 17.7% of the patients in the convalescent-plasma group. Glucocorticoids were administered to 466 patients (98.1%). At day 28, mortality was 35.4% in the convalescent-plasma group and 45.0% in the standard-care group (P = 0.03). In a prespecified analysis, this effect was observed mainly in patients who underwent randomization 48 hours or less after the initiation of invasive mechanical ventilation. Serious adverse events did not differ substantially between the two groups. CONCLUSIONS The administration of plasma collected from convalescent donors with a neutralizing antibody titer of at least 1:160 to patients with Covid-19-induced ARDS within 5 days after the initiation of invasive mechanical ventilation significantly reduced mortality at day 28. This effect was mainly observed in patients who underwent randomization 48 hours or less after ventilation initiation. (Funded by the Belgian Health Care Knowledge Center; ClinicalTrials.gov number, NCT04558476.).
PICO Summary
Population
Adult patients with Covid-19-induced acute respiratory distress syndrome (n= 475).
Intervention
Convalescent plasma (n= 237).
Comparison
Standard care (n= 238).
Outcome
At day 28, mortality was 35.4% in the convalescent-plasma group and 45.0% in the standard-care group. In a prespecified analysis, this effect was observed mainly in patients who underwent randomization 48 hours or less after the initiation of invasive mechanical ventilation. Serious adverse events did not differ substantially between the two groups.